The goal of this clinical trial is to learn if dexmedetomidine can reduce delirium in critically ill children, needing mechanical ventilation for more than 12 hours. The main question it aims to answer is : • Does dexmedetomidine reduce the proportion of children presenting at least one episode of delirium during their intensive care unit (ICU) stay ? Researchers will compare dexmetomidine to midazolam, to see if the use of dexmedetomidine reduces the prevalence of delirium. Participants will be sedated with midazolam or dexmedetomidine, according to randomization arm, and the rest of sedation is determined by the study protocol.
\- In the experimental group, participants will receive dexmedetomidine as primary sedative, with opioids for analgesia in order to reach sedation within the target range evaluated with the COMFORT B scale every 4 hours. The initial dose of dexmedetomidine continuous infusion is 0.7 µg/kg/h with increases of 0.2 µg/kg/h if needed associated to an opioid continuous infusion (sufentanil at 0.2 µg/kg/h or morphine at 40 µg/kg/h). A protocol to adjust level of sedation according to the COMFORT B scale will be followed with maximal doses of 1.4 µg/kg/h for dexmedetomidine, 1.5 µg/kg/h for sufentanil and 300 µg/kg/h for morphine. Other drugs like ketamine up to 2 mg/kg/h, propofol, other opioids, midazolam at bolus or small doses (beginning between 20 µg/kg/h and 0.5 mg/h according to age/weight) are possible and will be reported. \- In the control group, participants with invasive ventilation will receive midazolam as first line therapy with opioids in order to reach sedation within the target sedation range evaluated with the COMFORT B scale every 4 hours. The initial dose of midazolam is 40 µg/kg/h for children \<2 years, 60 µg/kg/h for children after 2 years, and 1 mg/h for children \>40kg associated with sufentanil at 0.2 µg/kg/h or intravenous morphine at 40 µg/kg/h. A protocol to adjust level of sedation according to the COMFORT B scale will be followed with maximal doses of 200 µg/kg/h and 10 mg/h if \>40kg for midazolam and 1.5 µg/kg/h for sufentanil or 300 mcg/kg/h for morphine. Other drugs like ketamine up to 2 mg/kg/h, propofol, other opioids, are possible and noted. In case of failure, addition of dexmedetomidine will be possible only if midazolam is used at maximal doses.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
266
Participants in intervention arm will receive dexmedetomidine as primary sedative. We will assess if there is less delirium in the intervention arm
participant will receive midazolam as the comparator group
CHU d'Angers
Angers, France
CHU de Caen
Caen, France
CHU de Lille
Lille, France
CHU de Marseille
Marseille, France
CHU de Nantes
Nantes, France
CHU de Strasbourg
Strasbourg, France
CHU de Tours
Tours, France
Proportion of children with at least one episode of delirium during the ICU stay.
Surveillance of delirium is part of the routine neurological monitoring in pediatric ICU. CAPD score is an 8-items scale. A score of 9 points or higher indicates the presence of delirium. We will evaluate the proportion of children with at least one CAPD score higher than 9.
Time frame: From enrollment to the end of ICU stay, up to 90 days
Sedation efficacy
Investigators will assess: * The percentage of sedation scores in the target sedation range evaluated with COMFORT B scale every 4 hours, in each group * Percentage of under-sedation, and adverse events (such as unplanned extubation with reintubation, accidental removal of a central line) * Percentage of over-sedation
Time frame: From enrollment to the end of sedation, up to 90 days
Duration of delirium
Investigators will assess the number of days with CAPD score higher than or equal to 9
Time frame: from enrollment to the end of ICU stay, up to 90 days
Adverse events and serious adverse events
Investigators will record: * Hypotension and/or bradycardia needing an intervention, unplanned extubation * accidental removal of a central line
Time frame: From enrollment to the end of ICU stay, up to 90 days
Mechanical ventilation
Investigators will report the mechanical ventilation time in hours
Time frame: From enrollment to extubation, for an average of 7 days
Health economic end points
Investigators will assess the cumulative doses of IV sedative and analgesic drugs so we can compare: * Difference in the costs of sedative, analgesics and opioids consumed during the paediatric intensive care stay and valued from the hospital perspective; * Difference in the cost of inpatient stays and the cost of stays in intensive care units valued from the healthcare system perspective, over a three month time horizon.
Time frame: From enrollment to the end of hospital stay, up to 90 days
Severity of delirium
Investigators will assess the severity of delirium defined by the need for antipsychotic drugs
Time frame: from enrollement to the end of hospital stay, up to 90 days
Need for re-intubation
Investigators will report the need for re-intubation post extubation
Time frame: from enrollment, to the end of hospital stay, up to 90 days
Need for neurological investigations
Investigators will report the percentage of brain imaging and electroencephalogramm
Time frame: from enrollement to the end of hospital stay, up to 90 days
Length of stay
Investigators will report * Intensive care unit length of stay, in days * Hospital length of stay out of the intensive care unit, in days
Time frame: from enrollement to the end of hospital stay, up to 90 days
Mortality
Investigators will assess: hospital mortality
Time frame: from enrollement, to the end of follow-up, up to 90 days
Withdrawal
Investigators will assess the incidence of iatrogenic withdrawal syndrome, measured with WAT-score (defined by WAT \> 4)
Time frame: from enrollement to the end of ICU stay, up to 90 days
Associated sedation
Investigators will assess the daily cumulative weight-adjusted dose of IV sedative agents (benzodiazepine, ketamine, propofol) and opioids required in each group.
Time frame: from enrollement, to the end of sedation, up to 90 days
Duration of sedation
Invesitgators will assess the number of days exposed to sedatives and opioids
Time frame: from enrollment, to the end of sedation, up to 90 days
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